rs202205643

Variant names:

• chr16-88428953-C-G
• rs202205643
• NM_001367624.2:c.1483C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-88428953-C-G
• chr16-88428953-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001367624.2(ZNF469):​c.1483C>G​(p.Pro495Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P495S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF469 NM_001367624.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.01
• Publications: 1 publications found

Genes affected

ZNF469 (HGNC:23216): (zinc finger protein 469) This gene encodes a zinc-finger protein. Low-percent homology to certain collagens suggests that it may function as a transcription factor or extra-nuclear regulator factor for the synthesis or organization of collagen fibers. Mutations in this gene cause brittle cornea syndrome. [provided by RefSeq, Jul 2008]

ZNF469 Gene-Disease associations (from GenCC):

• brittle cornea syndrome 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp
• brittle cornea syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• aortic disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

LOC112268182 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12084949).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367624.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF469	NM_001367624.2	MANE Select	c.1483C>G	p.Pro495Ala	missense	Exon 3 of 3	NP_001354553.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF469	ENST00000565624.3	TSL:6 MANE Select	c.1483C>G	p.Pro495Ala	missense	Exon 3 of 3	ENSP00000456500.2
	ZNF469	ENST00000437464.1	TSL:5	c.1483C>G	p.Pro495Ala	missense	Exon 1 of 2	ENSP00000402343.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 72

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Ehlers-Danlos syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.48	T
M_CAP	Pathogenic	0.78	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.0
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.039
Sift	Benign	0.20	T
Sift4G	Uncertain	0.0060	D
Vest4		0.12
MutPred		0.12		Loss of glycosylation at P495 (P = 0.0638)
MVP		0.14
ClinPred		0.15	T
GERP RS		2.5
gMVP		0.043
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs202205643; hg19: chr16-88495361;